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Genetic and cytogenetic analyses of refractory leukemia with chromothripsis, a new genomic abnormality

Research Project

Project/Area Number 16K10050
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionResearch Institute for Clinical Oncology, Saitama Cancer Center

Principal Investigator

Kawamura Machiko  埼玉県立がんセンター(臨床腫瘍研究所), 病院 血液内科, 医長 (80450592)

Co-Investigator(Kenkyū-buntansha) 金子 安比古  埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, その他 (50373387)
Research Collaborator TASHIRO Satoshi  広島大学, 原爆放射線医科学研究所, 教授 (20243610)
TAKI Tomohiko  杏林大学, 保健学部, 教授 (50322053)
HAYASHI Yasuhide  群馬県衛生環境研究所, 研究企画係, 研究員 (30238133)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords白血病 / クロモスリプシス / 思春期・若年成人 / SNPアレイ / 次世代シークエンス / PNA-FISH / 遺伝子
Outline of Final Research Achievements

We have demonstrated that there is a new oncogenic mechanism and the focus on chromothripsis ;a phenomenon in which chromosomes are shuttered at one time, deletion, a fusion gene, or proliferation occurs in the onset of some leukemias. SNP array CGH detected cases with chromothripsis. PNA (Peptide nucleic acid)-FISH could detect abnormalities of chromothripsis. The chromothripsis in leukemia is associated with the marker chromosome, dmin (double minutes), complex karyotype, 17p deletion, and in particular with TP53 gene mutation. The mechanisms underlying chromothripsis-associated AML are poorly understood, and treatment strategy is needed for the improvement of the patients’outcomes.

Academic Significance and Societal Importance of the Research Achievements

新たな発がん機構と注目されているクロモスリプシス;染色体が一度に粉砕され、融合遺伝子や遺伝子の一部の欠失、増殖が起きる現象が一部の白血病の発症に存在することを証明した。SNPアレイCGH法、クロモスリプシスの発症機序に関連のある染色体分裂の異常がわかるPNA-FISH法によりクロモスリプシス関連白血病を検出できた。これらは、染色体の特殊な異常 (marker 染色体、double minutes、17p欠失)、複雑な染色体異常と関連があり、特にがん抑制遺伝子TP53変異と関連があった。これらの症例は予後不良であり、この機序の解明により、治療対策をたてる必要があると考えられた。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (27 results)

All 2019 2018 2017 2016

All Journal Article (15 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 15 results,  Open Access: 8 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Combined Genetic and Chromosomal Characterization of Wilms Tumors Identifies Chromosome 12 Gain as a Potential New Marker Predicting a Favorable Outcome2019

    • Author(s)
      Haruta Masayuki、Arai Yasuhito、Okita Hajime、Tanaka Yukichi、Takimoto Tetsuya、Sugino Ryuichi P.、Yamada Yasuhiro、Kamijo Takehiko、Oue Takaharu、Fukuzawa Masahiro、Koshinaga Tsugumichi、Kaneko Yasuhiko
    • Journal Title

      Neoplasia

      Volume: 21 Issue: 1 Pages: 117-131

    • DOI

      10.1016/j.neo.2018.10.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recycling endosomal CD133 functions as an inhibitor of autophagy at the pericentrosomal region2019

    • Author(s)
      Hideki Izumi, Yuanyuan Li, Masami Shibaki, Daisuke Mori, Michio Yasunami, Seiji Sato, Hisashi Matsunaga, Takao Mae, Kenji Kodama, Takehiko Kamijo, Yasuhiko Kaneko & Akira Nakagawara
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 2236-2236

    • DOI

      10.1038/s41598-019-39229-8

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Recurrent CCND3 mutations in MLL-rearranged acute myeloid leukemia2018

    • Author(s)
      Matsuo Hidemasa、Itonaga Hidehiro、et al.
    • Journal Title

      Blood Advances

      Volume: 2 Issue: 21 Pages: 2879-2889

    • DOI

      10.1182/bloodadvances.2018019398

    • NAID

      120006534600

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 2.NM23 downregulation and lysophosphatidic acid receptor EDG2/lpa1 upregulation during myeloid differentiation of human leukemia cells.2018

    • Author(s)
      Okabe-Kado J, Hagiwara-Watanabe Y, Niitsu N, Kasukabe T, Kaneko Y.
    • Journal Title

      Leuk. Res.

      Volume: 66 Pages: 39-48

    • DOI

      10.1016/j.leukres.2018.01.003

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Outcome of renal tumors registered in Japan Wilms Tumor Study-2 (JWiTS-2): A report from the Japan Children's Cancer Group (JCCG)2018

    • Author(s)
      Koshinaga Tsugumichi、Takimoto Tetsuya、Oue Takaharu、Okita Hajime、Tanaka Yukichi、Nozaki Miwako、Tsuchiya Kunihiko、Inoue Eisuke、Haruta Masayuki、Kaneko Yasuhiko、Fukuzawa Masahiro
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 65 Issue: 7

    • DOI

      10.1002/pbc.27056

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Paternally inherited WT1 mutation plus uniparental disomy of 11p may be an essential mechanism for development of WT1-mutated familial Wilms tumor2018

    • Author(s)
      Sato Yuya、Haruta Masayuki、Kaneko Yasuhiko、Nakasato Yoshimasa、Kurosawa Hidemitsu、Yoshihara Shigemi
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 66 Issue: 1

    • DOI

      10.1002/pbc.27442

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia2017

    • Author(s)
      Yamato Genki、Yamaguchi Hiroki、Handa Hiroshi、Shiba Norio、Kawamura Machiko、Wakita Satoshi、Inokuchi Koiti、Hara Yusuke、Ohki Kentaro、Okubo Jun、Park Myoung-Ja、Sotomatsu Manabu、Arakawa Hirokazu、Hayashi Yasuhide
    • Journal Title

      Genes, Chromosomes and Cancer

      Volume: 56 Issue: 11 Pages: 800-809

    • DOI

      10.1002/gcc.22483

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] CD66c (KOR-SA3544) antigen expression of leukemic blasts in pediatric acute myeloid leukemia with TLS/FUS-ERG fusion transcript2017

    • Author(s)
      Kobayashi K.、Isobe K.、Hanada R.、Kawaguchi H.、Iwata T.、Kawamura M.
    • Journal Title

      International Journal of Laboratory Hematology

      Volume: 39 Issue: 6

    • DOI

      10.1111/ijlh.12714

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genomic analysis–integrated whole-exome sequencing of neuroblastomas identifies genetic mutations in axon guidance pathway2017

    • Author(s)
      Li Yuanyuan、Ohira Miki、Zhou Yong、Xiong Teng、Luo Wen、Yang Chao、Li Xiangchun、Gao Zhibo、Zhou Rui、Nakamura Yohko、Kamijo Takehiko、Kaneko Yasuhiko、Taketani Takeshi、Ueyama Junichi、Tajiri Tatsuro、Zhang Hongyan、Wang Jian、Yang Huanming、Yin Ye、Nakagawara Akira
    • Journal Title

      Oncotarget

      Volume: 8 Issue: 34 Pages: 56684-56697

    • DOI

      10.18632/oncotarget.18079

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] BRCA1 Alterations with Additional Defects in DNA Damage Response Genes May Confer Chemoresistance to BRCA-like Breast Cancers Treated with Neoadjuvant Chemotherapy.2017

    • Author(s)
      Takada M, Nagai S, Haruta M, Sugino RP, Tozuka K, Takei H, Ohkubo F, Inoue K, Kurosumi M, Miyazaki M, Sato-Otsubo A, Sato Y, Ogawa S, Kaneko Y.
    • Journal Title

      Genes Chromosomes Cancer.

      Volume: - Issue: 5 Pages: 405-420

    • DOI

      10.1002/gcc.22445

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development of a Sinple and Quick Immunochromatography Method for Detection of anti-HPV-16/-18 Antibodies2017

    • Author(s)
      Fumiko Endo, Tsutomu Tabata, Daichi Sadato, Machiko Kawamura, Noriyuki Ando, Keisuke Oboki, Masako Ukaji, Kaoru Kobayashi, Yukuharu Kobayashi, Tomoaki Ikeda and Futoshi Shibasaki
    • Journal Title

      PLoS One

      Volume: 12 Issue: 2 Pages: e0171314-e0171314

    • DOI

      10.1371/journal.pone.0171314

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma2017

    • Author(s)
      Fujiwara T, Uotani K, Yoshida A, Morita T, Nezu Y, Kobayashi E, Yoshida A5, Uehara T1, Omori T1, Sugiu K1, Komatsubara T, Takeda K, Kunisada T, Kawamura M, Kawai A, Ochiya T, Ozaki T
    • Journal Title

      Oncotarget

      Volume: - Issue: 20 Pages: 33375-33392

    • DOI

      10.18632/oncotarget.16498

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular cytogenetic characterization of two established ESFT cell lines2017

    • Author(s)
      Ishiguro M, Yuki M, Fukushige T, Mizoguchi M, Kaneko Y, Morishige T, Iwasaki H.
    • Journal Title

      Hum Cell

      Volume: 30 Issue: 1 Pages: 41-48

    • DOI

      10.1007/s13577-016-0145-7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical prognostic value of DNA methylation in hepatoblastoma: Four novel tumor suppressor candidates2016

    • Author(s)
      Honda S, Minato M, Suzuki H, Fujiyoshi M, Miyagi H, Haruta M, Kaneko Y, Hatanaka KC, Hiyama E, Kamijo T, Okada T, Taketomi A
    • Journal Title

      Cancer Science

      Volume: in press Issue: 6 Pages: 812-819

    • DOI

      10.1111/cas.12928

    • NAID

      120005828475

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Anaplastic histology Wilms' tumors registered to the Japan Wilms' Tumor Study Group are less aggressive than that in the National Wilms' Tumor Study 5.2016

    • Author(s)
      Oue T, Koshinaga T, Takimoto T, Okita H, Tanaka Y, Nozaki M, Haruta M, Kaneko Y, Fukuzawa M
    • Journal Title

      Pediatr Surg Int.

      Volume: 32 Issue: 9 Pages: 851-855

    • DOI

      10.1007/s00383-016-3929-7

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Chromothripsis-like Single Nucleotide Polymorphism array pattern in pediatric and adolescent acute leukemia2018

    • Author(s)
      Machiko Kawamura, Yasuhiko Kaneko, Naoto Fujita, Satoshi Tashiro
    • Organizer
      The 50th Annual Congress of the International Society of Paediatric Oncology ( SIOP 2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 思春期の難治性白血病におけるクロモスリプシス(染色体粉砕)の関連と病態解明2017

    • Author(s)
      川村眞智子
    • Organizer
      平成28年度 川野小児医学財団 助成研究成果発表会
    • Place of Presentation
      アルカディア市ヶ谷
    • Year and Date
      2017-03-04
    • Related Report
      2016 Research-status Report
  • [Presentation] Detection of chromothripsis by Single Nucleotide Polymorphism (SNP) Array in acute leukemia2017

    • Author(s)
      川村眞智子、久保田靖子、小林泰文、柵木信男、金子安比古
    • Organizer
      第79回日本血液学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Chromothripsis in refractory pediatric acute leukemia2017

    • Author(s)
      川村眞智子、金子安比古
    • Organizer
      第59回日本小児血液・がん学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] Incidence and state of high school students in adolescents and young adults with cancer in a single cancer center2017

    • Author(s)
      川村眞智子
    • Organizer
      第15回日本臨床腫瘍学会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Clinical significance of serum survivin levels in hematologic malignancies2017

    • Author(s)
      Machiko Kawamura, Junko Kado, You Nishimura, Yasuhiko Kaneko
    • Organizer
      29th World Congress of World Association of Societies of Pathology and Laboratory Medicine
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 成人のがん専門病院における思春期・若年成人のがんの疫学調査2016

    • Author(s)
      川村眞智子,上條岳彦、金子安比古
    • Organizer
      第58回 日本小児血液・がん学会学術集会
    • Place of Presentation
      品川プリンスホテル
    • Year and Date
      2016-12-15
    • Related Report
      2016 Research-status Report
  • [Presentation] Molecular and structural analyses in a case of coagulation factor XII deficiency2016

    • Author(s)
      Machiko Kawamura, Hiroaki Kawabe, Takeshi Beppu, Nobuko Kubota, Hirofumi Kobayashi, Nobuo Maseki, Yasuhiko Kaneko, Seiji Saito
    • Organizer
      第78回 日本血液学会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 当院における悪性リンパ腫遺伝子検査の現状2016

    • Author(s)
      小林 志帆, 新井 吉子, 赤木 究, 川村 眞智子, 黒住 昌史, 岩田 敏弘
    • Organizer
      第65回日本医学検査学会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2016-09-03
    • Related Report
      2016 Research-status Report
  • [Presentation] The serum survivin levels and pathological findings of diffuse large B-cell lymphoma2016

    • Author(s)
      Taguchi Y, Kawamura M, Okabe-Kado J, Tanaka H,Kawarai A, Nishimura Y, Kurosumi M, Iwata T
    • Organizer
      32nd World Congress of Biomedical Laboratory Science
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2016-08-31
    • Related Report
      2016 Research-status Report
  • [Presentation] 成人のがん専門病院における思春期若年成人のがん治療の現状2016

    • Author(s)
      川村眞智子、上條岳彦
    • Organizer
      第119回小児科学会学術集会
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2016-05-15
    • Related Report
      2016 Research-status Report
  • [Book] miRNAの最新知識―基礎領域から診断・治療応用まで2017

    • Author(s)
      落谷 孝広 (編集) 川村眞智子(分担)
    • Total Pages
      195
    • Publisher
      医薬ジャーナル社
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-07-01  

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